The long-range goal of this project is to learn how essential fatty acids (EFA) act in metabolic regulations, with special emphasis on whether EFA could act in regulating fatty acid synthesis by influencing hormone action through alteration in the composition of membrane phospholipids, especially the plasma membrane. EFA depletion, either in the EFA-deficient rat or in the rat in which the liver is EFA-depleted because of refeeding a high carbohydrate diet after fasting, results in elevated levels of the so-called "lipogenic enzymes", including glucose-6-phosphate dehydrogenase (G6PDH) and the fatty acid synthetase complex (FAS). EFA could act in regulation of fatty acid synthesis through their role as prostaglandin precursors, through acting as inhibitors of enzymes involved in fatty acid synthesis, through acting as part of repressor molecules which repress the genes for the so-called "lipogenic enzymes, or through influencing the action of hormones (which act in regulation of lipogenesis) by altering the composition and properties of membrane lipids, especially phospholipids. The approach we will use is to investigate the effects of EFA deficiency on the composition and properties of plasma membranes. It has been reported that EFA deficiency reduced the cholesterol level (as percent of total lipid) and increased the proportion of phospholipids (as percent of total lipid) in rat liver plasma membranes. We plan to re-investigate this report and then to compare the hormone- and calcium- binding of EFA-depleted and non-depleted liver plasma membranes, as well as their sensitivity to digitonin and phospholipase treatment. The ability of EFA to lower the levels of G6PDH and FAS in liver of EFA- deficient or fasted-refed rats will also be re-studied, under conditions where calorie intakes and carbohydrate intakes are equalized.